Synthesis and Composition of Neurolenin D Mesylate and Related Compounds - New Drugs for the Treatment of Parasitic Nematode Infections in Humans, Animals and Plants

Abstract

The natural product neurolenin D is isolated from Neurolaena lobata using continuous extraction, stirring over charcoal, flash column chromatography, and recrystallization. The secondary alcohol in this molecule is converted into a methane sulfonyl ester (mesylate) to generate a new molecule, neurolenin D mesylate. This previously unknown molecule has been tested for biological activity in assays for human toxicity, mutagenicity, and nematocidal potency. It is not toxic or mutagenic and demonstrates the ability to kill nematodes responsible for the neglected tropical disease lymphatic filariasis and is likely to have the same ability to kill other nematodes responsible for a wide range of diseases in humans, animals and plants. Additional esters of neurolenin D are claimed and procedures are outlined for their synthesis.

What is claimed is: 
     
         1 . A compound having the formula:
                       .   
     
     
         2 . A formulation comprising neurolenin D mesylate for the treatment of an organism suffering from a disease caused by an infection with a parasitic nematode, the organism selected from the group consisting of human, animal, and plant. 
     
     
         3 . A method of synthesizing neurolenin D mesylate comprising:
 reacting neurolenin D with mesyl chloride to form Neurolenin D mesylate.   
     
     
         4 . A method of treating an organism suffering from a disease caused by an infection with a parasitic nematode, the organism selected from the group consisting of human, animal, and plant, the method comprising administering to the organism a therapeutically effective dose of neurolenin D mesylate. 
     
     
         5 . The method of  claim 4  wherein the organism is a human. 
     
     
         6 . The method of  claim 4  wherein the organism is a companion animal. 
     
     
         7 . The method of  claim 4  wherein the organism is livestock. 
     
     
         8 . The method of  claim 4  wherein the organism is a plant. 
     
     
         9 . The method of  claim 4  wherein the parasitic nematode is a causative agent of a disease selected from the group consisting of lymphatic filariasis, elephantiasis, and river-blindness in humans. 
     
     
         10 . The method of  claim 4  wherein the parasitic nematode is a causative agent of heartworm in dogs. 
     
     
         11 . The method of  claim 4  wherein the parasitic nematode is a causative agent of a roundworm disease in livestock. 
     
     
         12 . A compound selected from the group consisting of:
                                                                                                                                                                                                                             .   
     
     
         13 . A formulation comprising one or more of the compounds of  claim 12  for the treatment of an organism suffering from a disease caused by a parasitic nematode, the organism selected from the group consisting of human, animal, and plant. 
     
     
         14 . A method of synthesizing neurolenin D esters comprising:
 reacting neurolenin D with a compound having a formula selected from the group consisting of
                     
                     
   wherein the reaction conditions include the presence of an amine base, and wherein R is selected from the group consisting of:
                     
                     
                     
                     
                     
                     
                     
                     
                     
 . 
   
     
     
         15 . The method according to  claim 14  wherein the compound reacting with neurolenin D has the formula
                     
 . 
 
     
     
         16 . The method according to  claim 14 , wherein the compound reacting with neurolenin D has the formula
                       .   
     
     
         17 . The method according to  claim 14 , wherein the amine base is selected from the group consisting of pyridine, Diazabicycloundecene (DBU), imidazole, 4-Dimethylaminopyridine (DMAP), and 1,4-Diazabicyclo[2.2.2]octane (DABCO). 
     
     
         18 . A method of treating an organism suffering from a disease caused by an infection with a parasitic nematode, the organism selected from the group consisting of human, animal, and plant, the method comprising administering a therapeutically effective dose of one or more of the compounds of  claim 12 . 
     
     
         19 . The method of  claim 18  wherein the organism is a human. 
     
     
         20 . The method of  claim 18  wherein the organism is a companion animal. 
     
     
         21 . The method of  claim 18  wherein the organism is livestock. 
     
     
         22 . The method of  claim 18  wherein the organism is a plant. 
     
     
         23 . The method of  claim 18  wherein the parasitic nematode is a causative agent of a disease selected from the group consisting of lymphatic filariasis, elephantiasis, and river-blindness in humans. 
     
     
         24 . The method of  claim 18  wherein the parasitic nematode is a causative agent of heartworm in dogs. 
     
     
         25 . The method of  claim 18  wherein the parasitic nematode is a causative agent of a roundworm disease in livestock.